title: GABA in the paraventricular nucleus tonically suppresses baroreflex function: alterations during pregnancy.
abstract: It is well established that GABAergic inputs to the paraventricular nucleus of the hypothalamus (PVN) tonically suppress heart rate and the activity of several sympathetic nerves. However, whether GABA similarly inhibits PVN control of baroreflex function has not been previously investigated. To test this hypothesis, it was determined whether microinjection of the GABA(A) antagonist, bicuculline, into the PVN enhances the baroreflex in anesthetized female virgin rats. In addition, because GABAergic inhibition of PVN preautonomic neurons is decreased during pregnancy, it was also determined whether the effects of PVN bicuculline administration on baroreflex function were less in pregnant animals. In virgin rats, PVN microinjection of bicuculline increased (P < 0.05) baroreflex gain and maximum levels of heart rate (gain, from 1.6 ± 0.6 to 3.8 ± 1.3 bpm/mmHg; maximum, from 406 ± 18 to 475 ± 14 bpm) and of lumbar sympathetic nerve activity (gain from 2.6 ± 0.7 to 4.8 ± 1.6%/mmHg; maximum, 149 ± 32 to 273 ± 48%), indicating that PVN GABA normally suppresses baroreflex function. Pregnancy decreased heart rate baroreflex gain (pregnant, 0.9 ± 0.3 bpm/mmHg; virgin, 1.9 ± 0.2 bpm/mmHg; P < 0.05). Following PVN bicuculline administration in pregnant rats, smaller (P < 0.01) increments in baroreflex gain (pregnant, 0.6 ± 0.1 bpm/mmHg; virgin, 2.4 ± 0.9 bpm/mmHg) and maximum (pregnant, 33 ± 7 bpm; virgin, 75 ± 12 bpm; P < 0.05) were produced. Collectively, these data suggest that the PVN normally inhibits the baroreflex via tonic GABAergic inputs and that this inhibition is less during pregnancy.
authors.affiliation: Department of Physiology and Pharmacology, Oregon Health & Science University, Portland, 97239, USA.
authors.forename: Mollie C
authors.initials: MC
authors.lastname: Page
authors.forename: Priscila A
authors.initials: PA
authors.lastname: Cassaglia
authors.forename: Virginia L
authors.initials: VL
authors.lastname: Brooks
mesh_terms: D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D001640:Bicuculline / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D058787:GABA-A Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008845:Microinjections; D023421:Models, Animal; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000187:drug effects / Q000378:metabolism*
chemical_list: D058787:GABA-A Receptor Antagonists; D005680:gamma-Aminobutyric Acid; D001640:Bicuculline